Is EBF2 p.Leu73Val (c.217C>G) pathogenic?

EBF2 p.Leu73Val (c.217C>G) is classified Uncertain significance in EBF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: ambiguous (0.4214); Ultra-rare (popmax 0.0117%, amr).

How common is EBF2 p.Leu73Val (c.217C>G) in the general population?

EBF2 p.Leu73Val (c.217C>G) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about EBF2 p.Leu73Val (c.217C>G)?

AlphaMissense predicts ambiguous (score 0.4214) — an in-silico prediction, not a clinical call.

EBF2 p.Leu73Val

c.217C>G · rs1001855163 · VCV2241000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4214 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Computational evidence

Protein change
AlphaMissense	0.4214	ambiguous
REVEL	0.365	indeterminate
SaProt	LLR -9.64	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.99, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 4,216 bp · p 0.34 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0117% Admixed American · 7/60,004 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000496% 8/1,614,072 alleles · ultra-rare exomes 2/1,461,878 · genomes 6/152,194 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,572
African / African-American	0.00133%	74,930

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: EBF2
Protein: p.Leu73Val
Coding: c.217C>G
MANE Select: NM_022659
dbSNP: rs1001855163
Type: single nucleotide variant
Location: chr8:26042166 (GRCh38)
Gene constraint: LOEUF 0.394 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.38

Full EBF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EBF2 c.1164+4A>G Benign ★★ same type
EBF2 p.Lys352= Benign ★★ same type
EBF2 p.Ala420Thr Uncertain significance ★ ⚠ same type
EBF2 p.Ala47Gly Uncertain significance ★ ⚠ same type
EBF2 p.Ala47Ser Uncertain significance ★ ⚠ same type
EBF2 p.Ala555Thr Uncertain significance ★ ⚠ same type
EBF2 p.Ala87Thr Uncertain significance ★ ⚠ same type
EBF2 p.Arg128Ser Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ebf2-p-leu73val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown